Extracellular Vesicle miRNAs in Diagnostics of Gastric Cancer.

Gastric cancer (GC) poses a significant global health challenge because of its high mortality rate attributed to the late-stage diagnosis and lack of early symptoms. Early cancer diagnostics is crucial for improving the survival rates in GC patients, which emphasizes the importance of identifying GC markers for liquid biopsy. The review discusses a potential use of extracellular vesicle microRNAs (EV miRNAs) as biomarkers for the diagnostics and prognostics of GC. Methods. Original articles on the identification of EV miRNA as GC markers published in the Web of Science and Scopus indexed issues were selected from the PubMed and Google Scholar databases. We focused on the methodological aspects of EV analysis, including the choice of body fluid, methods for EV isolation and validation, and approaches for EV miRNA analysis. Conclusions. Out of 33 found articles, the majority of authors investigated blood-derived extracellular vesicles (EVs); only a few utilized EVs from other body fluids, including tissue-specific local biofluids (washing the tumor growth areas), which may be a promising source of EVs in the context of cancer diagnostics. GC-associated miRNAs identified in different studies using different methods of EV isolation and analysis varied considerably. However, three miRNAs (miR-10b, miR-21, and miR-92a) have been found in several independent studies and shown to be associated with GC in experimental models. Further studies are needed to determine the optimal miRNA marker panel. Another essential step necessary to improve the reliability and reproducibility of EV-based diagnostics is standardization of methodologies for EV handling and analysis of EV miRNA.

Evaluation of Octopus maya enzyme activity of the digestive gland and gastric juice.

BACKGROUND: As the demand for Octopus maya grows, sustainable farming practices become essential to prevent overexploitation. Thus, its farming development can be a sustainable alternative to traditional fishing. Understanding the digestive dynamics is essential for devising optimal dietary formulations in aquaculture, particularly the role of enzymes like cathepsins and others. Despite the progress in understanding cephalopod digestion, little is known about the specific functioning of the digestive enzymes responsible for breaking down protein substrates. This knowledge gap underscores the need for further research to ensure O. maya population sustainable management. METHODS AND RESULTS: Dietary formulations are identified for cephalopods by characterizing O. maya digestive enzymes present in the digestive gland and gastric juice. The present investigation revealed that acidic proteases showed a peak activity at higher temperatures than alkaline proteases. Inhibitors confirmed the presence of H, L, and D cathepsins. Noteworthy is a lower activation energy of alkaline enzymes compared to acidic, ones highlighting an intriguing aspect of O. maya's digestive physiology. CONCLUSION: Overall, this research provides valuable insights into O. maya digestive enzyme functions representing a significant advancement in formulating diets crucial for octopus successful farming that may help to fully understand its physiology.

Elucidation of Degradation Behavior of Barbiturates in Artificial Gastric Juice: Study on Degradability of Drugs in Stomach (V).

The gastric stability of eight barbiturates (BARs) (barbital, primidone, allobarbital, phenobarbital, cyclobarbital, pentobarbital, secobarbital, and thiobutabarbital (TBB)) was examined in artificial gastric juice using LC/UV detection. Among the eight BARs, only TBB was degraded at higher temperatures. Furthermore, the degradation product of TBB was isolated, structurally analyzed, and finally identified as 5-butan-2-yl-5-ethyl-1,3-diazinane-2,4,6-trione, also known as butabarbital. The study elucidated that butabarbital was formed by substituting the sulfur atom of the carbonyl group at the 2-position of TBB with an oxygen atom under acidic condition.

Intra- and interindividual variability in fasted gastric content volume.

BACKGROUND: Gastric fluid plays a key role in food digestion and drug dissolution, therefore, the amount of gastric fluid present in a fasted state may influence subsequent digestion and drug delivery. We aimed to describe intra- and interindividual variation in fasted gastric content volume (FGCV) and to determine the association with age, sex, and body size characteristics. METHODS: Data from 24 MRI studies measuring FGCV in healthy, mostly young individuals after an overnight fast were pooled. The analysis included 366 participants who had up to 6 repeated measurements, with a total of 870 measurements. Linear mixed model analysis was performed to calculate intra- and interindividual variability and to assess the effects of age, sex, weight, height, weight*height as a proxy for body size, and body mass index (BMI). RESULTS: FGCV ranged from 0 to 156 mL, with a mean (± SD) value of 33 ± 25 mL. The overall coefficient of variation within the study population was 75.6%, interindividual SD was 15 mL, and the intraindividual SD was 19 mL. Age, weight, height, weight*height, and BMI had no effect on FGCV. Women had lower volumes compared to men (MD: -6 mL), when corrected for the aforementioned factors. CONCLUSION: FGCV is highly variable, with higher intraindividual compared to interindividual variability, indicating that FGCV is subject to day-to-day and within-day variation and is not a stable personal characteristic. This highlights the importance of considering FGCV when studying digestion and drug dissolution. Exact implications remain to be studied.

Volatilomic profiles of gastric juice in gastric cancer patients.

Volatilomics is a powerful tool capable of providing novel biomarkers for the diagnosis of gastric cancer. The main objective of this study was to characterize the volatilomic signatures of gastric juice in order to identify potential alterations induced by gastric cancer. Gas chromatography with mass spectrometric detection, coupled with headspace solid phase microextraction as the pre-concentration technique, was used to identify volatile organic compounds (VOCs) released by gastric juice samples collected from 78 gastric cancer patients and two cohorts of controls (80 and 96 subjects) from four different locations (Latvia, Ukraine, Brazil, and Colombia). 1440 distinct compounds were identified in samples obtained from patients and 1422 in samples provided by controls. However, only 6% of the VOCs exhibited an incidence higher than 20%. Amongst the volatiles emitted, 18 showed differences in their headspace concentrations above gastric juice of cancer patients and controls. Ten of these (1-propanol, 2,3-butanedione, 2-pentanone, benzeneacetaldehyde, 3-methylbutanal, butylated hydroxytoluene, 2-pentyl-furan, 2-ethylhexanal, 2-methylpropanal and phenol) appeared at significantly higher levels in the headspace of the gastric juice samples obtained from patients; whereas, eight species showed lower abundance in patients than found in controls. Given that the difference in the volatilomic signatures can be explained by cancer-related changes in the activity of certain enzymes or pathways, the former set can be considered potential biomarkers for gastric cancer, which may assist in developing non-invasive breath tests for the diagnosis of this disease. Further studies are required to elucidate further the mechanisms that underlie the changes in the volatilomic profile as a result of gastric cancer.

Identification of Autoantigens in Pediatric Gastric Juices.

Purpose: This study aimed to investigate the presence of autoantigens in the gastric juices of children. Methods: Gastric juice and serum samples were obtained from 53 children <15 years of age who underwent gastric endoscopy. Among these, 8, 22, and 23 participants were in the age groups 0-5, 6-10, and 11-15 years, respectively. These samples were analyzed using two-dimensional electrophoresis (2-DE), immunoblot analysis, and matrix-assisted laser desorption ionization-time of-flight mass spectrometry. Furthermore, we reviewed the histopathological findings and urease test results and compared them with the results of 2-DE and immunoblot analysis. Results: There were no statistically significant differences in urease test positivity, grades of chronic gastritis, active gastritis, or Helicobacter pylori infiltration of the antrum and body among the three age groups. Three distinct patterns of gastric juice were observed on 2-DE. Pattern I was the most common, and pattern III was not observed below the age of 5 years. Histopathological findings were significantly different among active gastritis (p=0.037) and H. pylori infiltration (p=0.060) in the gastric body. The immunoblots showed large spots at an approximate pH of 3-4 and molecular weights of 31-45 kDa. These distinct, large positive spots were identified as gastric lipase and pepsin A and C. Conclusion: Three enzymes, which are normally secreted under acidic conditions were identified as autoantigens. Further investigation of the pathophysiology and function of autoantigens in the stomach is required.

Graded diagnosis of Helicobacter pylori infection using hyperspectral images of gastric juice.

Helicobacter pylori is a potential underlying cause of many diseases. Although the Carbon 13 breath test is considered the gold standard for detection, it is high cost and low public accessibility in certain areas limit its widespread use. In this study, we sought to use machine learning and deep learning algorithm models to classify and diagnose H. pylori infection status. We used hyperspectral imaging system to gather gastric juice images and then retrieved spectral feature information between 400 and 1000 nm. Two different data processing methods were employed, resulting in the establishment of one-dimensional (1D) and two-dimensional (2D) datasets. In the binary classification task, the random forest model achieved a prediction accuracy of 83.27% when learning features from 1D data, with a specificity of 84.56% and a sensitivity of 92.31%. In the ternary classification task, the ResNet model learned from 2D data and achieved a classification accuracy of 91.48%.

Can Gastric Juice Analysis with EndoFaster® Reduce the Environmental Impact of Upper Endoscopy?

Gastrointestinal (GI) endoscopy services are in third place as major contributors to CO2 emissions among healthcare facilities, especially due to their massive waste production. One of the measures suggested to reduce this environmental impact is a reduction in histological examinations performed on biopsy specimens taken during endoscopy. A reliable candidate to reduce the rate of biopsies and, consequently, the impact of CO2 emissions could be EndoFaster®, an innovative medical device that allows one to suspect or rule out both H. pylori infection and precancerous lesions on the gastric mucosa by analyzing a small amount of gastric juice aspirated during endoscopy in real time. In the present study, we investigated the ability of EndoFaster® to reduce the environmental impact of upper endoscopy, comparing the CO2 production of standard biopsy sampling as suggested in guidelines and biopsies guided by real-time EndoFaster® results during endoscopy. By estimating an overall 90% rate of biopsies according to standard guidelines and a reduction of 50% of gastric biopsies based on EndoFaster® results, we calculated a 44% overall reduction in CO2 emissions, demonstrating that by using this tool, it is possible to distinctly reduce the contribution of upper endoscopy to global warming.

Evaluating the effect of food components on the digestion of dietary nucleic acids in human gastric juice in vitro.

Nucleic acids (NAs) were recently shown to be digested by pepsin in vitro; however, NAs digestion in human gastric juice in vivo is more complicated because of the complex gastric environment and ingestion of other food components. The purpose of this study was to investigate the digestibility of NAs in real human gastric juices after ingestion of other food components. As a result, DNA digestion was not affected when carbohydrates, proteins, and metal elements were ingested within the recommended dietary intake levels. Separately, protein exerted an inhibitory effect on DNA digestion when the mass ratio of protein:DNA was greater than 40:1. DNA exists in the nucleoprotein, which is closer to the state of DNA in real food, and was digested efficiently in human gastric juice. Meanwhile, DNA digestion was rarely affected even when the concentrations of monovalent ion (Na+) and divalent ions (Mg2+) were as high as 500 and 100 mM, respectively, and high concentration of Mg2+ ranged from 20 to 100 mM accelerated the digestion. In particular, short-stranded DNA (<100 nt) and miRNAs (19 ~ 25 nt) were not obviously degraded in human gastric juice. In conclusion, dietary NAs were digested efficiently and were not affected by other food components in human gastric juice, which may facilitate further digestion and utilization of DNA in the intestinal tract.

Vitamin C modulates adrenaline-augmented gastric injury via cardiac troponin/creatine kinase pathway in Wistar rats.

Objectives: Vitamin C has anti-oxidant benefits in the gastrointestinal tract and heart. This study investigated the effect of vitamin C on some gastric parameters in myocardial injury in rats. Materials and Methods: Thirty Wistar rats were divided into five groups (n = 6). Group 1 was the control and Group 2 (ADR) received 1 mg/kg of adrenaline subcutaneously on days 13 and 14. Group 3 received vitamin C (200 mg/kg) orally for 14 days. Group 4 received adrenaline (1 mg/kg) on days 1 and 2 and vitamin C from days 1 to 14. Group 5 received vitamin C till day 14 and adrenaline on days 13 and 14. All animals were sacrificed after 2 hr of pyloric ligation. Gastric secretion parameters were assessed while a blood sample was obtained for biochemical analysis. Results: Gastric juice volume, total gastric acidity, pepsin activity, cardiac troponin 1, creatine kinase-MB, and lactate dehydrogenase levels increased (P<0.05) in ADR only group relative to the control. Pre- and post-vitamin C treatment reduced (P<0.05) these markers to near normal. However, treatment with vitamin C reduced (P<0.05) ulcer score, and increased (P<0.05) pepsin activity, mucus weight, and serum vitamin C levels when compared with the ADR-only group. Pre-treatment with vitamin C resulted in a marked decrease (P<0.05) in gastric juice volume, pepsin activity, and total gastric acidity compared with post-treatment in the adrenaline-induced injury group. Conclusion: Vitamin C pretreatment reduces excessive gastric secretions, ulcer scores, and attenuates cardio-inflammatory responses in adrenaline-augmented myocardial injury in rats.

Colonization of the gastric juice by Candida spp. promotes surgical site infection after hepatectomy.

PURPOSE: Candida spp. cause opportunistic infections in conditions of immunodeficiency. Here, we investigated the relationship between colonization of the gastric juice by Candida spp. and surgical site infection (SSI) in hepatectomy. METHODS: Consecutive hepatectomy cases between November 2019 and April 2021 were enrolled. Gastric juice samples (collected intraoperatively through a nasogastric tube) were cultured. We compared factors related to patient background, blood test findings, surgical findings, and postoperative complications between the Candida + group (positive for colonization of the gastric juice by Candida spp.) and the Candida - group (negative). In addition, we identified the factors that contribute to SSI. RESULTS: There were 29 and 71 patients in the Candida + and Candida - groups, respectively. The Candida + group was significantly older (average age: Candida + 74 years vs. Candida - 69 years; p = 0.02) and contained more patients negative for the hepatitis B and C virus (Candida + 93% vs. Candida - 69%; p = 0.02). SSI was significantly more common in the Candida + group (Candida + 31% vs. Candida - 9%; p = 0.01). Postoperative bile leakage and colonization of the gastric juice by Candida spp. were independent predictors of SSI. CONCLUSION: Colonization of the gastric juice by Candida spp. is a risk factor for SSI after hepatectomy.

The Human Gastric Juice: A Promising Source for Gastric Cancer Biomarkers.

Gastric cancer (GC) is a major public health problem worldwide, with high mortality rates due to late diagnosis and limited treatment options. Biomarker research is essential to improve the early detection of GC. Technological advances and research methodologies have improved diagnostic tools, identifying several potential biomarkers for GC, including microRNA, DNA methylation markers, and protein-based biomarkers. Although most studies have focused on identifying biomarkers in biofluids, the low specificity of these markers has limited their use in clinical practice. This is because many cancers share similar alterations and biomarkers, so obtaining them from the site of disease origin could yield more specific results. As a result, recent research efforts have shifted towards exploring gastric juice (GJ) as an alternative source for biomarker identification. Since GJ is a waste product during a gastroscopic examination, it could provide a "liquid biopsy" enriched with disease-specific biomarkers generated directly at the damaged site. Furthermore, as it contains secretions from the stomach lining, it could reflect changes associated with the developmental stage of GC. This narrative review describes some potential biomarkers for gastric cancer screening identified in gastric juice.

Exploring the Cholesterol-Modifying Abilities of Lactobacilli Cells in Digestive Models and Dairy Products.

This study aimed to investigate the ability of lactic acid bacteria to remove cholesterol in simulated gastric and intestinal fluids. The findings showed that the amount of cholesterol removed was dependent on the biomass, viability, and bacterial strain. Some cholesterol binding was stable and not released during gastrointestinal transit. The presence of cholesterol affected the fatty acid profile of bacterial cells, potentially influencing their metabolism and functioning. However, adding cholesterol did not significantly impact the survival of lactic acid bacteria during gastrointestinal transit. Storage time, passage, and bacterial culture type did not show significant effects on cholesterol content in fermented dairy products. Variations in cell survival were observed among lactic acid bacteria strains in simulated gastric and intestinal fluids, depending on the environment. Higher milk protein content was found to be more protective for bacterial cells during gastrointestinal transit than fat content. Future research should aim to better understand the impact of cholesterol on lactic acid bacteria metabolism and identify potential health benefits.

Gastric juice non-coding RNAs as potential biomarkers for gastric cancer.

Gastric cancer (GC), being one of the most common malignant human tumors, occupies the second position in the structure of mortality in men and women. High rates of morbidity and mortality in this pathology determine its extremely high clinical and social significance. Diagnosis and timely treatment of precancerous pathology is the main way to reduce morbidity and mortality, and early detection of GC and its adequate treatment improve prognosis. The ability to accurately predict the development of GC and start treatment on time, as well as the ability to determine the stage of the disease if the diagnosis is confirmed - non-invasive biomarkers can become the key to solving these and many other problems of modern medicine. One of the promising biomarkers being studied are non-coding RNAs, namely, miсroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). They are involved in a wide range of processes, including apoptosis, proliferation, differentiation, angiogenesis, which play a critical role in the development of GC oncogenesis. In addition, they are quite specific and stable due to their carriers (extracellular vesicles or Argonaute 2 protein) and can be detected in various human biological fluids, in particular gastric juice. Thus, miRNAs, lncRNAs, and circRNAs isolated from the gastric juice of GC patients are promising preventive, diagnostic and prognostic non-invasive biomarkers. This review article presents the characteristics of circulating or extracellular miRNAs, lncRNAs, and circRNAs in gastric juice, allowing their use in the GC preventive, diagnosis, prognosis and monitoring therapy.

Elucidation of Degradation Behavior of Hydroxy Group-Containing Benzodiazepines in Artificial Gastric Juice: Study on Degradability of Drugs in Stomach (III).

The degradation behavior of three benzodiazepines (BZPs)-lormetazepam (LMZ), lorazepam, and oxazepam-with hydroxy groups on the diazepine ring in artificial gastric juice and the effect of storage pH conditions on drug degradability were monitored using an LC/photodiode array detector (PDA) to estimate their pharmacokinetics in the stomach. Although the three BZPs degraded in artificial gastric juice, none could be restored, despite increasing the storage pH, implying that the degradation reaction was irreversible. As for LMZ, we discussed the physicochemical parameters, such as the activation energy and activation entropy involved in the degradation reaction as well as the reaction kinetics; one of the degradation products was isolated and purified for structural analysis. In the LMZ degradation experiment, peaks corresponding to degradation products, (A) and (B), were detected through the LC/PDA measurements. Regarding the degradation behavior, we hypothesized that LMZ was degraded into (B) via (A), where (A) was an intermediate and (B) was the final product. Although the isolation of degradation product (A) was challenging, degradation product (B) could be isolated and was confirmed to be "methanone, [5-chloro-2-(methylamino)phenyl](2-chlorophenyl)-" based on structure determination using various instrumental analyses. The compound exhibited axis asymmetry as determined using single-crystal X-ray structure analysis. Because the formation of degradation product (B) was irreversible, it would be prudent to target the final degradation product (B) and LMZ for identification when detecting LMZ in human stomach contents, such as during forensic dissection.

Intraprocedural gastric juice analysis as compared to rapid urease test for real-time detection of Helicobacter pylori.

BACKGROUND: Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy (UGE) to perform gastric juice analysis and real-time detection of Helicobacter pylori (H. pylori). AIM: To assess the diagnostic performance of this technology and its impact on the management of H. pylori in the real-life clinical setting. METHODS: Patients undergoing routine UGE were prospectively recruited. Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test (RUT). Gastric juice sampling and analysis was performed using the Endofaster, and the diagnosis of H. pylori was based on real-time ammonium measurements. Histological detection of H. pylori served as the diagnostic gold standard for comparing Endofaster-based H. pylori diagnosis with RUT-based H. pylori detection. RESULTS: A total of 198 patients were prospectively enrolled in an H. pylori diagnostic study by Endofaster-based gastric juice analysis (EGJA) during the UGE. Biopsies for RUT and histological assessment were performed on 161 patients (82 men and 79 women, mean age 54.8 ± 19.2 years). H. pylori infection was detected by histology in 47 (29.2%) patients. Overall, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) for H. pylori diagnosis by EGJA were 91.5%, 93.0%, 92.6%, 84.3%, and 96.4%, respectively. In patients on treatment with proton pump inhibitors, diagnostic sensitivity was reduced by 27.3%, while specificity and NPV were unaffected. EGJA and RUT were comparable in diagnostic performance and highly concordant in H. pylori detection (κ-value = 0.85). CONCLUSION: Endofaster allows for rapid and highly accurate detection of H. pylori during gastroscopy. This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.

Analysis of bacterial diversity and community structure in gastric juice of patients with advanced gastric cancer.

BACKGROUND: The occurrence and development of gastric cancer are related to microorganisms, which can be used as potential biomarkers of gastric cancer. OBJECTIVE: To screen the microbiological markers of gastric cancer from the microorganisms of gastric juice. METHODS: Gastric juice samples were collected from 61 healthy people and 78 patients with gastric cancer (48 cases of early gastric cancer and 30 cases of advanced gastric cancer). The bacterial 16 S rRNA V1-V4 region of gastric juice samples was sequenced. The Shannon index, Simpson index, Ace index and Chao index were used to analyze the diversity of gastric juice samples. The RDP classifier Bayesian algorithm was used to analyze the community structure of 97% OTU representative sequences with similar levels. Linear discriminant analysis and ST-test were used to analyze the differences. Six machine learning algorithms, including the logistic regression algorithm, random forest algorithm, neural network algorithm, support vector machine algorithm, Catboost algorithm and gradient lifting tree algorithm, were used to construct risk prediction models for gastric cancer and advanced gastric cancer. RESULTS: The microbiota diversity and the abundance of bacteria was different in the healthy group, early gastric cancer and advanced gastric cancer (P < 0.05). The top five abundant bacteria among the three groups were Streptococcus, Rhodococcus, Prevotella, Pseudomonas and Helicobacter. Bacterial flora such as Streptococcus, Rhodococcus and Ochrobactrum were significantly different between the healthy group and the gastric cancer group. The accuracy of the random forest prediction model is the highest (82.73% correct). The bacteria with the highest predictive value included Streptococcus, Lactobacillus and Ochrobactrum. The abundance of bacteria such as Fusobacterium, Capnocytophaga, Atopobium, Corynebacterium was high in the advanced gastric cancer group. CONCLUSION: Gastric juice bacteria can be used as potential biomarkers to predict the occurrence and development of gastric cancer.

Negligible procedure-related dissemination risk of mucosal incision-assisted biopsy for gastrointestinal stromal tumors versus endoscopic ultrasound-guided fine-needle aspiration/biopsy.

BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64% of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100%) and EUS-FNAB (97.1%) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

Gastric cancer detection by non-blood-based liquid biopsies: A systematic review looking into the last decade of research.

Gastric cancer (GC) screening is arguable in most Western countries. Liquid biopsies are a great promise to answer the unmet need for less invasive diagnostic biomarkers in GC. Thus, we aimed at systematically reviewing the current knowledge on liquid biopsy-based biomarkers in GC screening. A systematic search on PubMed/MEDLINE and Scopus databases was performed on published articles reporting the use of non-blood specimen (saliva, gastric juice [GJ], urine and stool) on GC diagnosis. 3208 records were retrieved by June 2022. After removal of duplicate records, 2379 abstracts were screened, and 84 full texts included in this systematic review. More than 90% of studies were reported on Asian populations. Overall, 9 studies explored stool-, 12 saliva-, and 29 urine-derived biomarkers for GC detection. Additionally, 37 studies, representing the majority, analyzed GJ, focusing on nucleic acid molecules. Several miRNAs and lncRNA molecules have been associated with GC risk, particularly miR-21 (area under the curve [AUC] = 0.97, 95% CI: 0.94-1.00). Considering salivary biomarkers, the best described model in validation sets included the soybean agglutinin and Vicia villosa agglutinin lectins (AUC = 0.89, 95% CI: 0.80-0.99). Most studies in urine carried out metabolomic approaches, with two discriminatory models presenting AUC values superior to 0.97. This systematic review emphasizes the potential role of non-blood-based biomarkers, although further validation, particularly in Western countries, is mandatory, namely for non-invasive screening and/or monitoring, as well as the use of GJ as a tool to enhance upper gastrointestinal endoscopy accuracy.

Daily requirement of softgel thyroxine is independent from gastric juice pH.

Background: Softgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better performance of softgel LT4 preparation in patients with gastric disorders but whether this finding is related to gastric juice pH variation in vivo is not known. Methods: Twenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 µg/kg/day) and with stable thyroid stimulating hormone (TSH) values on target (<0.8-2.5> mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar individual serum TSH value. All subjects followed a specific treatment schedule, taking LT4 in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent endoscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gastric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients. Results: Upon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly reduced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction >20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p<0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p<0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman's ρ =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman's ρ =1.952; p = 0.3194). Conclusions: These findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with increased LT4 requirement, owed to disorders impairing the gastric acidic output.